MX2007009099A - Tratamiento de tumores con metastasis. - Google Patents
Tratamiento de tumores con metastasis.Info
- Publication number
- MX2007009099A MX2007009099A MX2007009099A MX2007009099A MX2007009099A MX 2007009099 A MX2007009099 A MX 2007009099A MX 2007009099 A MX2007009099 A MX 2007009099A MX 2007009099 A MX2007009099 A MX 2007009099A MX 2007009099 A MX2007009099 A MX 2007009099A
- Authority
- MX
- Mexico
- Prior art keywords
- compound
- cancer
- subject
- tumor
- patient
- Prior art date
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- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000006711 vascular endothelial growth factor production Effects 0.000 description 1
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 1
- 229950000578 vatalanib Drugs 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000012130 whole-cell lysate Substances 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US64756805P | 2005-01-27 | 2005-01-27 | |
| US66924505P | 2005-04-06 | 2005-04-06 | |
| US72205305P | 2005-09-29 | 2005-09-29 | |
| PCT/US2006/002979 WO2006081445A2 (en) | 2005-01-27 | 2006-01-27 | Treatment of metastasized tumors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2007009099A true MX2007009099A (es) | 2007-09-13 |
Family
ID=36741085
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2007009099A MX2007009099A (es) | 2005-01-27 | 2006-01-27 | Tratamiento de tumores con metastasis. |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US20060183750A1 (enExample) |
| EP (2) | EP1845990B1 (enExample) |
| JP (2) | JP5371246B2 (enExample) |
| KR (1) | KR101387985B1 (enExample) |
| CN (1) | CN103893181A (enExample) |
| AT (1) | ATE526025T1 (enExample) |
| AU (1) | AU2006208012B2 (enExample) |
| BR (1) | BRPI0607285A2 (enExample) |
| CA (1) | CA2596084A1 (enExample) |
| CY (1) | CY1112570T1 (enExample) |
| DK (1) | DK1845990T3 (enExample) |
| ES (2) | ES2374570T3 (enExample) |
| IL (1) | IL184866A0 (enExample) |
| MA (1) | MA29266B1 (enExample) |
| MX (1) | MX2007009099A (enExample) |
| NO (1) | NO20074360L (enExample) |
| PL (2) | PL2301546T3 (enExample) |
| PT (2) | PT1845990E (enExample) |
| SG (1) | SG173317A1 (enExample) |
| SI (1) | SI2301546T1 (enExample) |
| TN (1) | TNSN07294A1 (enExample) |
| WO (1) | WO2006081445A2 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2334641T3 (es) | 2000-09-01 | 2010-03-15 | Novartis Vaccines And Diagnostics, Inc. | Derivados aza heterociclicos y su uso terapeutico. |
| ES2250480T3 (es) | 2000-09-11 | 2006-04-16 | Chiron Corporation | Derivados de quinolinona como inhibidores de tirosina quinasa. |
| BR0313743A (pt) | 2002-08-23 | 2005-07-05 | Chiron Corp | Benzimidazol quinolinonas e usos destas |
| DK1885187T3 (da) * | 2005-05-13 | 2013-12-09 | Novartis Ag | Fremgangsmåde til behandling af lægemiddelresistent cancer |
| JP2008542289A (ja) * | 2005-05-23 | 2008-11-27 | ノバルティス アクチエンゲゼルシャフト | ４−アミノ−５−フルオロ−３−［６−（４−メチルピペラジン−１イル）−１ｈ−ベンズイミダゾール−２−イル］−１ｈ−キノリン−２−オン乳酸塩の結晶およびその他の形態 |
| AR070924A1 (es) * | 2008-03-19 | 2010-05-12 | Novartis Ag | Formas cristalinas y dos formas solvatadas de sales del acido lactico de 4- amino -5- fluoro-3-(5-(4-metilpiperazin-1-il ) -1h- bencimidazol-2-il) quinolin -2-(1h) - ona |
| EP2432451A2 (en) * | 2009-05-20 | 2012-03-28 | Children's Medical Center Corporation | Compositions for the treatment of metastatic cancer and methods of use thereof |
| RU2012148710A (ru) | 2010-04-16 | 2014-05-27 | Новартис Аг | Органическое соединение для применения при лечении рака печени |
| WO2012158994A1 (en) * | 2011-05-19 | 2012-11-22 | Novartis Ag | 4-amino-5-fluoro-3- [6- (4 -methylpiperazin- 1 - yl) - 1h - benzimidazol - 2 - yl] - 1h - quinoli n-2-one for use in the treatment of adenoid cystic carcinoma |
| MX2014009303A (es) * | 2012-01-31 | 2014-10-14 | Novartis Ag | Combinacion de un inhibidor de rtk con un anti-estrogeno y uso del mismo para el tratamiento de cancer. |
| EP3484881B1 (en) * | 2016-07-14 | 2020-04-29 | Bristol-Myers Squibb Company | Bicyclic heteroaryl substituted compounds |
Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3663606A (en) * | 1966-06-21 | 1972-05-16 | Mitsui Toatsu Chemicals | Organic imino-compounds |
| DE2363459A1 (de) | 1973-12-20 | 1975-06-26 | Basf Ag | Neue fluoreszierende chinolinverbindungen |
| US4659657A (en) * | 1982-12-24 | 1987-04-21 | Bayer Aktiengesellschaft | Chromogenic and fluorogenic esters for photometric or fluorimetric determination of phosphatases or sulphatases |
| US5073492A (en) * | 1987-01-09 | 1991-12-17 | The Johns Hopkins University | Synergistic composition for endothelial cell growth |
| JPH0699497B2 (ja) | 1987-04-16 | 1994-12-07 | 富士写真フイルム株式会社 | 光重合性組成物 |
| DE3932953A1 (de) * | 1989-10-03 | 1991-04-11 | Boehringer Mannheim Gmbh | Neue 2-bicyclo-benzimidazole, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| GB9108547D0 (en) | 1991-04-22 | 1991-06-05 | Fujisawa Pharmaceutical Co | Quinoline derivatives |
| US5710158A (en) * | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| US5480883A (en) * | 1991-05-10 | 1996-01-02 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| USRE37650E1 (en) * | 1991-05-10 | 2002-04-09 | Aventis Pharmacetical Products, Inc. | Aryl and heteroaryl quinazoline compounds which inhibit CSF-1R receptor tyrosine kinase |
| US5856115A (en) * | 1991-05-24 | 1999-01-05 | Fred Hutchinson Cancer Research Center | Assay for identification therapeutic agents |
| CA2452130A1 (en) * | 1992-03-05 | 1993-09-16 | Francis J. Burrows | Methods and compositions for targeting the vasculature of solid tumors |
| JP3142378B2 (ja) | 1992-06-22 | 2001-03-07 | ティーディーケイ株式会社 | 有機ｅｌ素子 |
| US5792771A (en) * | 1992-11-13 | 1998-08-11 | Sugen, Inc. | Quinazoline compounds and compositions thereof for the treatment of disease |
| US5981569A (en) * | 1992-11-13 | 1999-11-09 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Substituted phenylacrylonitrile compounds and compositions thereof for the treatment of disease |
| US5763441A (en) * | 1992-11-13 | 1998-06-09 | Sugen, Inc. | Compounds for the treatment of disorders related to vasculogenesis and/or angiogenesis |
| JPH0743896A (ja) | 1993-07-28 | 1995-02-14 | Toyobo Co Ltd | 光重合性組成物 |
| JPH0829973A (ja) | 1994-07-11 | 1996-02-02 | Toyobo Co Ltd | 光重合性組成物 |
| JP3441246B2 (ja) | 1995-06-07 | 2003-08-25 | 富士写真フイルム株式会社 | 光重合性組成物 |
| GB9624482D0 (en) * | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| DE19610723A1 (de) | 1996-03-19 | 1997-09-25 | Bayer Ag | Elektrolumineszierende Anordnungen unter Verwendung von Blendsystemen |
| US5942385A (en) * | 1996-03-21 | 1999-08-24 | Sugen, Inc. | Method for molecular diagnosis of tumor angiogenesis and metastasis |
| JP4373497B2 (ja) * | 1996-06-19 | 2009-11-25 | ローン−プーラン・ロレ・リミテツド | 置換されたアザビシクロ化合物、ならびにｔｎｆおよびサイクリックａｍｐホスホジエステラーゼ産生の阻害剤としてのそれらの使用 |
| IL127559A0 (en) | 1996-06-20 | 1999-10-28 | Univ Texas | Compounds and methods for providing pharmacologically active preparations and uses thereof |
| US6111110A (en) * | 1996-10-30 | 2000-08-29 | Eli Lilly And Company | Synthesis of benzo[f]quinolinones |
| EP1226119B1 (en) | 1999-10-19 | 2005-03-16 | MERCK & CO. INC. | Tyrosine kinase inhibitors |
| KR100681724B1 (ko) | 1999-10-19 | 2007-02-28 | 머크 앤드 캄파니 인코포레이티드 | 티로신 키나제 억제제 및 이를 포함하는 약제학적 조성물 |
| WO2001062252A1 (en) | 2000-02-25 | 2001-08-30 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US6420382B2 (en) * | 2000-02-25 | 2002-07-16 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US6313138B1 (en) * | 2000-02-25 | 2001-11-06 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| ES2334641T3 (es) * | 2000-09-01 | 2010-03-15 | Novartis Vaccines And Diagnostics, Inc. | Derivados aza heterociclicos y su uso terapeutico. |
| AU2001288432A1 (en) * | 2000-09-01 | 2002-03-22 | Icos Corporation | Materials and methods to potentiate cancer treatment |
| US20030028018A1 (en) * | 2000-09-11 | 2003-02-06 | Chiron Coporation | Quinolinone derivatives |
| ES2250480T3 (es) * | 2000-09-11 | 2006-04-16 | Chiron Corporation | Derivados de quinolinona como inhibidores de tirosina quinasa. |
| JP2004536113A (ja) * | 2001-07-03 | 2004-12-02 | カイロン コーポレイション | チロシンキナーゼおよびセリン／スレオニンキナーゼのインヒビターとしてのインダゾールベンズイミダゾール化合物 |
| BR0313743A (pt) * | 2002-08-23 | 2005-07-05 | Chiron Corp | Benzimidazol quinolinonas e usos destas |
| US7825132B2 (en) * | 2002-08-23 | 2010-11-02 | Novartis Vaccines And Diagnostics, Inc. | Inhibition of FGFR3 and treatment of multiple myeloma |
| US7838527B2 (en) | 2002-11-13 | 2010-11-23 | Novartis Vaccines And Diagnostics, Inc. | Methods of treating cancer and related methods |
| US6774327B1 (en) * | 2003-09-24 | 2004-08-10 | Agilent Technologies, Inc. | Hermetic seals for electronic components |
| CA2544186A1 (en) * | 2003-11-07 | 2005-05-26 | Chiron Corporation | Inhibition of fgfr3 and treatment of multiple myeloma with benzimidazole quinolinones |
| WO2005082340A2 (en) * | 2004-02-20 | 2005-09-09 | Chiron Corporation | Modulation of inflammatory and metastatic processes |
| US20060261307A1 (en) * | 2005-05-18 | 2006-11-23 | Black D J | Water Activated Organic Scavenger |
| KR102639757B1 (ko) | 2017-01-09 | 2024-02-23 | 엘지이노텍 주식회사 | 카메라 모듈 및 이를 포함하는 광학기기 |
-
2006
- 2006-01-27 EP EP06733986A patent/EP1845990B1/en not_active Not-in-force
- 2006-01-27 PL PL10186757T patent/PL2301546T3/pl unknown
- 2006-01-27 PT PT06733986T patent/PT1845990E/pt unknown
- 2006-01-27 WO PCT/US2006/002979 patent/WO2006081445A2/en not_active Ceased
- 2006-01-27 EP EP10186757.0A patent/EP2301546B1/en not_active Revoked
- 2006-01-27 SI SI200631858T patent/SI2301546T1/sl unknown
- 2006-01-27 SG SG2011046166A patent/SG173317A1/en unknown
- 2006-01-27 ES ES06733986T patent/ES2374570T3/es active Active
- 2006-01-27 BR BRPI0607285-2A patent/BRPI0607285A2/pt not_active IP Right Cessation
- 2006-01-27 AU AU2006208012A patent/AU2006208012B2/en not_active Ceased
- 2006-01-27 JP JP2007553278A patent/JP5371246B2/ja not_active Expired - Fee Related
- 2006-01-27 PT PT101867570T patent/PT2301546E/pt unknown
- 2006-01-27 KR KR1020077019428A patent/KR101387985B1/ko not_active Expired - Fee Related
- 2006-01-27 CN CN201410121175.8A patent/CN103893181A/zh active Pending
- 2006-01-27 AT AT06733986T patent/ATE526025T1/de active
- 2006-01-27 US US11/342,257 patent/US20060183750A1/en not_active Abandoned
- 2006-01-27 PL PL06733986T patent/PL1845990T3/pl unknown
- 2006-01-27 ES ES10186757.0T patent/ES2525670T3/es active Active
- 2006-01-27 MX MX2007009099A patent/MX2007009099A/es not_active Application Discontinuation
- 2006-01-27 CA CA002596084A patent/CA2596084A1/en not_active Abandoned
- 2006-01-27 DK DK06733986.1T patent/DK1845990T3/da active
-
2007
- 2007-07-26 IL IL184866A patent/IL184866A0/en unknown
- 2007-07-27 TN TNP2007000294A patent/TNSN07294A1/en unknown
- 2007-08-23 MA MA30162A patent/MA29266B1/fr unknown
- 2007-08-27 NO NO20074360A patent/NO20074360L/no not_active Application Discontinuation
-
2009
- 2009-12-31 US US12/650,725 patent/US20100173873A1/en not_active Abandoned
-
2011
- 2011-12-06 CY CY20111101216T patent/CY1112570T1/el unknown
-
2013
- 2013-06-20 JP JP2013129277A patent/JP2013177464A/ja not_active Withdrawn
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Legal Events
| Date | Code | Title | Description |
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| FA | Abandonment or withdrawal |